Role of MicroRNA-98 in targeting IRS-2, Regulation of Insulin Signaling and Glucose Uptake in the Liver after Bariatric Surgery

Abstract

Background: Dysregulation of microRNA expression in various tissues and body fluids has been associated with several diseases, including Type 2 Diabetes Mellitus (T2DM). In this study, we measured the difference in the expression of microRNA in liver tissue of db/+ and db/db mice. And then, we hypothesized that bariatric(gastric bypass) surgery could change expression of a certain microRNA which may contribute to insulin resistance in obesity or T2DM. Methods: We make use of db/+ and db/db to make moldes of bariatric surgery, then we examine the expression of microRNA after surgery camparing sham surgery. Using Luciferase assay we confirmed that microRNA-98 which may be related to the insulin resistance directly targets IRS-2 3'UTR. MicroRNA levels were measured by real-time PCR in db/db mice. Insulin signaling was detected by immunoblotting and glcose uptake. Involvement of IRS2 was studied with microRNA mimics and inhibitor. The role of microRNA in vivo was explored with microRNA antagomir. Results: MicroRNA-98(miR-98) is decreased after bariatric surgery. Meanwhile we demenstrated that microRNA-98 increased in the liver of db/db mice campairing with db/+ mice. Overexpression of miR-98 decreases IRS2 protein levelsand activity and inhibition of miR-98 by antisense oligonucleotides operaincreases IRS2 protein levels and activity. MicroRNA-98 can also affect the uptake of glucose in insulin-resistance cultured hepG2 cells. In addition, inhibition of miR-98 by antagomir improve the level of blood glucose in db/db mice through mediating expression of IRS2 protein. Conclusion: We infirmed that microRNA-98 was related to bariaitric surgey and it was up-regulated in db/db mice, and played a key role in insulin resistance by inhibiting IRS-2 protein expression. These findings provide novel insights into the molecular basis of insulin resistance, and implicate bariatric surgery may change change the expression of microRNA to improve insulin resistance.